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Topics associated with the chemical sciences form a significant part of the curriculum in science at the primary school level in the U.K. In this methodology paper, we demonstrate how a wide range of research articles associated with the chemical sciences can be disseminated to an elementary school audience and how children can carry out investigations associated with cutting-edge research in the classroom. We discuss how the Primary Science Teaching Trust's (PSTT's) "I bet you did not know" (IBYDK) articles and their accompanying Teacher Guides benefit children, primary (elementary) school teachers, and other stakeholders including the researchers themselves. We define three types of research articles; ones describing how children can reproduce the research themselves without much adaptation, others where children can mirror the research using similar methods, and some where an analogy can be used to explain the research. We provide exemplars of each type and some preliminary feedback on articles written.

Climate change is of great concern to all age groups but in particular to children. "Simple" climate models have been in place for a long time and can be used effectively with post-16 students. For younger children, modifications are required, and we describe in this paper the development and use of two such models. The first (the Granny Model) is a pictorial version of the model that has been used extensively with primary and early secondary school aged children (14 and younger). The second is an online version of the simple climate model that can be used without recourse to the underpinning mathematics and science but allows children to experiment with changing variables and how these changes affect the average surface temperature of the Earth.

All learners have a contribution to make to the development of the Chemical Sciences, be that in novel ways to teach, and their perspectives and contexts, but also in research, both in chemical education and the wider Chemical Sciences. Through four case studies, this paper explores interactions with diverse groups and how this has altered perspectives on both teaching and research. The case studies include work with visually impaired adults, a project bringing together First Peoples in Australia with academics to explore old ways (traditional science) and new ways (modern approaches), primary (elementary) school perspectives on teaching science, and a project in South Africa to connect university and township communities. Not only do these case studies demonstrate the immense value these diverse groups bring to our understanding about how to learn, but they also bring new perspectives on how to view and solve chemical problems.

Postgraduate engagement in delivering outreach activities is more commonplace than it once was. However, the impact on postgraduate students (typically studying for a Ph.D. degree) of participating in the delivery of these outreach activities has rarely, if ever, been recorded. The Bristol ChemLabS Outreach program has been running for ca. 17 years, and in that time, many postgraduate students have been involved (approximately 500), with around 250 typically for up to 3 years. We sought to investigate the impact of outreach engagement on postgraduate alumni who were involved in the program for over 3 years (32) and how the experiences and training of the outreach program had impacted on their careers postgraduation. Thirty of the 32 postgraduates engaged and ~70% reported that their outreach experience had influenced their decision making on future careers. Many respondents reported that the skills and experiences gained through outreach participation had contributed to success in applying for and interviewing at their future employers. All respondents reported that outreach had helped them to develop key skills that were valued in the workplace, specifically, communication, teamwork, organizational skills, time planning, event planning, and event management. Rather than a pleasant distraction or an opportunity to supplement income, all participants noted that they felt there were many additional benefits and that this was time well spent. Outreach should not be viewed as a distraction to science research but rather an important enhancement to it provided that the program is well constructed and seeks to develop those delivering the outreach activities.

Little is known about parents' perceptions of school counselling in Hong Kong. We adopted an explanatory sequential mixed methods design to investigate Chinese and non-Chinese parents' perceptions. In phase one, 287 parents in Hong Kong were surveyed. Results suggested that Chinese parents had a poorer understanding of counsellors' roles, more negative perceptions of counselling, and were less likely to perceive counselling as beneficial than did non-Chinese parents. In phase two, we interviewed 27 parents. Our findings suggested that cultural stigma and school-related factors accounted for the findings of the phase one study. Schools may consider proactive engagement with parents, and establishing communication which is sensitive to cultural norms to promote a better understanding of and willingness to participate in counselling.

School counselling is a well-established means of supporting the mental health of children. Counsellors are most effective when they collaborate with parents, so it is important that parents have a good understanding of and access to school counselling services. Despite this, little is known about parents' perceptions of counselling in Hong Kong schools. We interviewed 27 parents in Hong Kong to investigate how they perceived the counselling services provided by their children's local and international schools, and analysed the data thematically. International school parents recognised the potential of school counselling as a means of support for their children and wanted to work more closely with counsellors to a greater extent than local school parents. Parents were confused about the roles of counsellors and experienced stigma and concerns about confidentiality which inhibited them from engaging with counselling services. Our findings suggest that school principals should work with counsellors to establish and communicate roles more clearly. Greater recognition of counsellors' professionalism, and clearer role differentiation between counsellors and other mental health and educational professionals may improve parental engagement with and support for school counselling.

Rationale & Objective: Cilastatin is an inhibitor of drug metabolism in the proximal tubule that demonstrates nephroprotective effects in animals. It has been used in humans in combination with the antibiotic imipenem to block imipenem’s renal metabolism. This systematic review and meta-analysis evaluated the nephroprotective effects of cilastatin in humans. Study Design: Systematic review and meta-analysis of observational (comparative effectiveness) studies or randomized clinical trials (RCTs). Setting & Study Populations: People of any age at risk of acute kidney injury (AKI). Selection Criteria for Studies: We systematically searched MEDLINE, Embase, Web of Science, and the Cochrane Controlled Trials registry from database inception to November 2023 for observational studies or RCTs that compared kidney outcomes among groups treated with cilastatin, either alone or as combination imipenem-cilastatin, versus an inactive or active control group not treated with cilastatin. Data Extraction: Two reviewers independently evaluated studies for inclusion and risk of bias. Analytical Approach: Treatment effects were estimated using random-effects models, and heterogeneity was quantified using the I2 statistic. Results: We identified 10 studies (5 RCTs, n = 531 patients; 5 observational studies, n = 6,321 participants) that met the inclusion criteria, including 4 studies with comparisons to inactive controls and 6 studies with comparisons to alternate antibiotics. Based on pooled results from 7 studies, the risk of AKI was lower with imipenem-cilastatin (risk ratio [RR], 0.52; 95% confidence intervals [CI], 0.40-0.67; I2 = 26.5%), with consistent results observed in RCTs (3 RCTs, RR, 0.26; 95% CI, 0.09-0.77; I2 = 44.4%) and observational studies (4 studies, RR, 0.54; 95% CI, 0.41-0.72; I2 = 44.4%). Based on results from 6 studies, serum creatinine concentration was lower following treatment with imipenem-cilastatin than comparators (weighted mean difference in serum creatinine −0.14 mg/dL (95% CI, −0.21 to −0.07; I2 = 0%). The overall certainty of the evidence was low due to heterogeneity of the results, high risk of bias, and indirectness among the identified studies. Limitations: Clinical and statistical heterogeneity could not be fully explained due to a limited number of studies. Conclusions: Patients treated with imipenem-cilastatin developed AKI less frequently and had lower serum creatinine concentration following treatment than control groups or those who had received comparator antibiotics. Larger clinical trials with less risk of detection bias due to lack of allocation concealment and blinding are needed to establish the efficacy of cilastatin for AKI prevention. Plain-Language Summary: Cilastatin, used with the antibiotic imipenem, has shown kidney-protective effects in animals and preclinical studies of acute kidney injury (AKI). This systematic review and meta-analysis identified 10 studies (5 randomized controlled trials and 5 observational studies) of imipenem-cilastatin involving people at risk of AKI. Pooled estimates of treatment effects indicated that patients who received imipenem-cilastatin had a lower incidence of AKI and lower serum creatinine concentrations following treatment compared to comparator groups. Despite these promising findings, the overall certainty of the evidence was low due to heterogeneity among studies, high risk of bias, and indirectness of the data. Although cilastatin appears to be a promising medication for preventing AKI, larger, well-designed trials are needed to establish its effectiveness.

Purpose of Review: Diabetes is the most common cause of kidney disease in individuals that receive a kidney transplant, and those without pre-existing diabetes are at greater risk of developing diabetes following kidney transplant. A class of diabetes treatment medications called glucagon-like peptide-1 receptor agonists (GLP-1RA) has seen recent widespread use for people with diabetes or obesity, with efficacy for improved glycemic control, weight loss, and reduced risk of cardiovascular events. Given these benefits, and indications for use that often co-occur in kidney transplant recipients, use of GLP-1RAs warrants consideration in this population. Therefore, we sought to review the current literature to better understand the mechanisms of action, clinical application, and person-centred considerations of GLP-1RAs in kidney transplant recipients. Sources of Information: Original articles were identified between December 2023 and July 2024 from electronic databases including the Ovid MEDLINE database, PubMed, and Google Scholar using terms “kidney transplant,” “GLP-1,” “glucagon-like peptide-1 receptor agonist,” and “diabetes.” Methods: A comprehensive review of the literature was conducted to explore the relationship between GLP-1RAs and kidney transplant recipients. We reviewed the current state of evidence across the research disciplines of basic or fundamental science, clinical and health services research, and person-centred equity science, and highlighted important knowledge gaps that offer opportunities for future research. Key Findings: Numerous clinical studies have demonstrated the benefit of GLP-1RAs in people with and without diabetic kidney disease, including decreased risk of cardiovascular events. However, there is a paucity of high-quality randomized controlled trials and observational studies analyzing use of GLP-1RAs in kidney transplant recipients. Evidence of benefit in this population is therefore limited to small studies or inferred from research conducted in nontransplant populations. Growing evidence from preclinical and clinical studies may elucidate renoprotective mechanisms of GLP-1RAs and remove barriers to application of these drugs in the transplant recipient population. Individuals who are female, non-white, have lower socioeconomic status, and live in rural communities are at greater risk of diabetes and have lower uptake of GLP-1RAs. There is a need for clinical trials across diverse kidney transplant populations to estimate the efficacy of GLP-1RAs on important health outcomes. Limitations: The search strategy for this narrative review may not have been sensitive to identify all relevant articles. Our search was limited to English language articles.

Atmospheric electricity measurements, principally of the hourly potential gradient (PG), were made continuously at Eskdalemuir Observatory, Scotland (55.314° N, 3.206° W), between 1911 and 1981. Air ion properties were also determined. The sensing apparatus for PG measurement at Eskdalemuir initially used a Kelvin water dropper potential equaliser (1911–1936), followed by a radioactive probe from 1936 and, from 1965, a horizontal stretched wire sensor at 0.5 m, all attached to recording devices. Monthly mean PG data from these instruments are now available digitally. Originally, the data were classified into undisturbed and disturbed days, using the chart record (electrogram). This approach has deficiencies at Eskdalemuir due to mist, fog and calm conditions, which can influence the mean PG despite the day appearing undisturbed on the electrogram. Nevertheless, a correlation with Pacific Ocean temperature fluctuations is apparent in the Eskdalemuir PG data between 1911 and 1950. As at Lerwick, there was an abrupt decrease in the PG caused by nuclear weapon detonations in the late 1950s and early 1960s. The 1950s PG decrease began at Eskdalemuir before that at Lerwick, for which possible additional local factors are evaluated.

Summary: Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. Methods: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. Findings: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. Interpretation: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. Funding: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Abstract Background and Aims High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower‐extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association. Methods Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (23Na‐MRI) and proton (1H‐MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic‐euglycemic clamp. Results Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high‐sensitivity C‐reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high‐sensitivity C‐reactive protein and interleukin‐6 (p for interaction = 0.022 and 0.006, respectively). Conclusions Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation.

School counselling has the potential to deliver significant support for the wellbeing of children. However, much of the research on school counsellors has been conducted in developed Western countries, with very limited research into factors influencing the effectiveness of counsellors in lower middle-income countries or in Asia. The aim of this qualitative study was to investigate the perceptions of Filipino counsellors about their roles, and factors that supported or impeded their effectiveness. Seventeen school counsellors in the Philippines were interviewed, and the data were analysed thematically. Our findings suggest that Filipino school counsellors often carry out dual roles, experience a lack of role clarity, and are systemically disempowered in their schools. Relationships with school principals have a significant influence on counsellors' roles and positioning in schools, and therefore on their effectiveness. The ability of principals to foster a school ethos supportive of counselling is essential in enabling counsellors to leverage the multifunctional nature of their work, become embedded and centrally positioned in the school community, and enhance their effectiveness. Doing so can enable counselling to be more culturally accessible to young people.

Abstract The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

Abstract Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. In vitro, LeY CAR T cells directly killed organoids derived from androgen receptor (AR)-positive or AR-null PDXs. In vivo, although LeY CAR T cells alone did not reduce tumor growth, a single prior dose of carboplatin reduced tumor burden. Carboplatin had a pro-inflammatory effect on the TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and re-oriented M1 macrophage differentiation. In a PDX less sensitive to carboplatin, CAR T cell infiltration was dampened; however, a reduction in tumor burden was still observed with increased T cell activation. These findings indicate that carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME.

Background: The kidney failure risk equation (KFRE) can be used to predict progression to end-stage kidney disease in a clinical setting. Objective: Evaluate implementation of a formalized risk-based approach in nephrologists’ outpatient clinics and multidisciplinary chronic kidney disease (CKD) clinics to determine candidacy for multidisciplinary care, and the impact of CKD care selection on clinical outcomes. Design: Population-based descriptive cohort study. Setting: Alberta Kidney Care South. Patients: Adults attending or considered for a multidisciplinary CKD clinic between April 1, 2017, and March 31, 2019. Measurements: Exposure —The course of CKD care assigned by the nephrologist: management at multidisciplinary CKD clinic; management by a nephrologist or primary care physician. Primary Outcome —CKD progression, defined as commencement of kidney replacement therapy (KRT). Secondary Outcomes —Death, emergency department visits, and hospitalizations. Methods: We linked operational data from the clinics (available until March 31, 2019) with administrative health and laboratory data (available until March 31, 2020). Comparisons among patient groups, courses of care, and clinical settings with negative binomial regression count models and calculated unadjusted and fully adjusted incidence rate ratios. For the all-cause death outcome, we used Cox survival models to calculate unadjusted and fully adjusted hazard ratios. Results: Of the 1748 patients for whom a KFRE was completed, 1347 (77%) remained in or were admitted to a multidisciplinary CKD clinic, 310 (18%) were managed by a nephrologist only, and 91 (5%) were referred back for management by their primary care physician. There was a much higher kidney failure risk among patients who remained at or were admitted to a multidisciplinary CKD clinic (median 2-year risk of 34.7% compared with 3.6% and 0.8% who remained with a nephrologist or primary care physician, respectively). None of the people managed by their primary care physician alone commenced KRT, while only 2 (0.6%) managed by a nephrologist without multidisciplinary CKD care commenced KRT. The rates of emergency department visits, hospitalizations, and death were lower in those assigned to management outside the multidisciplinary CKD clinics when compared with those managed in the multidisciplinary care setting. Limitations: The follow-up period may not have been long enough to determine outcomes, and potentially limited generalizability given variability of care in multidisciplinary clinics. Conclusions: Our findings indicate that a portion of patients can be directed to less resource-intensive care without a higher risk of adverse events. Trial registration: Not applicable.

Background: Despite efforts to provide evidence-based care for people living with kidney disease, health care provider goals and priorities are often misaligned with those of individuals with lived experience of disease. Coupled with competing interests of time, resources, and an abundance of suitable guideline topics, identifying and prioritizing areas of focus for the Canadian nephrology community with a patient-oriented perspective is necessary and important. Similar priority-setting exercises have been undertaken to establish research priorities for kidney disease and to standardize outcomes for kidney disease research and clinical care; however, research priorities are distinct from priorities for guideline development. Inclusion of people living with health conditions in the selection and prioritization of guideline topics is suggested by patient engagement frameworks, though the process to operationalizing this is variable. We propose that the Canadian Society of Nephrology Clinical Practice Guideline Committee (CSN CPGC) takes the opportunity at this juncture to incorporate evidence-based prioritization exercises with involvement of people living with kidney disease and their caregivers to inform future guideline activities. In this protocol, we describe our planned research methods to address this. Objective: To establish consensus-based guideline topic priorities for the CSN CPGC using a modified Delphi survey with involvement of multidisciplinary stakeholders, including people living with kidney disease and their caregivers. Study design: Protocol for a Modified Delphi Survey. Setting: Pilot-tested surveys will be distributed via email and conducted using the online platform SurveyMonkey, in both French and English. Participants: We will establish a group of multidisciplinary clinical and research stakeholders (both within and outside CSN membership) from Canada, in addition to people living with kidney disease and/or their caregivers. Methods: A comprehensive literature search will be conducted to generate an initial list of guideline topics, which will be organized into three main categories: (1) International nephrology-focused guidelines that may require Canadian commentary, (2) Non-nephrology specific guidelines from Canada that may require CSN commentary, and (3) Novel topics for guideline development. Participants will engage in a multi-round Modified Delphi Survey to prioritize a set of “important guideline topics.” Measures: Consensus will be reached for an item based on both median score on the Likert-type scale (≥ 7) and the percentage agreement (≥ 75%); the Delphi process will be complete when consensus is reached on each item. Guideline topics will then be given a priority score calculated from the total Likert ratings across participants, adjusted for the number of participants. Limitations: Potential limitations include participant response rates and compliance to survey completion. Conclusions: We propose to incorporate evidence-based prioritization exercises with the engagement of people living with kidney disease and their caregivers to establish consensus-based guideline topics and inform future guidelines activities of the CSN CPGC.

Background Sodium (Na+) stored in skin and muscle tissue is associated with essential hypertension. Sodium magnetic resonance imaging is a validated method of quantifying tissue stores of Na+. In this study, we evaluated tissue Na+ in patients with elevated blood pressure or stage I hypertension in response to diuretic therapy or low Na+ diet. Methods and Results In a double‐blinded, placebo‐controlled trial, patients with systolic blood pressure 120 to 139 mm Hg were randomized to low sodium diet (